ID MED25_HUMAN Reviewed; 747 AA. AC Q71SY5; A8K095; B9TX30; O95783; Q6P143; Q6QMH5; Q707U4; Q8TB55; Q9H0L5; AC Q9HB34; DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 02-OCT-2007, sequence version 2. DT 27-MAR-2024, entry version 146. DE RecName: Full=Mediator of RNA polymerase II transcription subunit 25; DE AltName: Full=Activator interaction domain-containing protein 1; DE AltName: Full=Activator-recruited cofactor 92 kDa component; DE Short=ARC92; DE AltName: Full=Mediator complex subunit 25; DE AltName: Full=p78; GN Name=MED25; Synonyms=ACID1, ARC92, PTOV2; ORFNames=TCBAP0758; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=12163014; DOI=10.1016/s0006-291x(02)00872-0; RA Wang C., McCarty I.M., Balazs L., Li Y., Steiner M.S.; RT "A prostate-derived cDNA that is mapped to human chromosome 19 encodes a RT novel protein."; RL Biochem. Biophys. Res. Commun. 296:281-287(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, RP IDENTIFICATION IN THE MEDIATOR COMPLEX, INTERACTION WITH VP16, ASSOCIATION RP WITH PROMOTER REGIONS, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=14657022; DOI=10.1093/emboj/cdg619; RA Mittler G., Stuehler T., Santolin L., Uhlmann T., Kremmer E., RA Lottspeich F., Berti L., Meisterernst M.; RT "A novel docking site on Mediator is critical for activation by VP16 in RT mammalian cells."; RL EMBO J. 22:6494-6504(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-11; 197-207; 241-254; RP 398-446 AND 520-530, FUNCTION, IDENTIFICATION IN THE MEDIATOR COMPLEX, RP INTERACTION WITH VP16, AND TISSUE SPECIFICITY. RX PubMed=14983011; DOI=10.1073/pnas.0308676100; RA Yang F., DeBeaumont R., Zhou S., Naeaer A.M.; RT "The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a RT functionally important target of the VP16 transcriptional activator."; RL Proc. Natl. Acad. Sci. U.S.A. 101:2339-2344(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), AND ALTERNATIVE SPLICING. RA Kivil A., Kazantseva A., Vinkel K.J.M., Sadam H., Neuman T., Palm K.; RT "Alternative splicing as a prevalent mechanism in regulating mammalian RT mediator tail subcomplex activity."; RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 159-747 (ISOFORM 5). RC TISSUE=Eye, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 180-747 (ISOFORM 4). RC TISSUE=Leukocyte; RA Villalon D.K., Luna R.A., Margolin J.K., Tsang Y.T.M., Hale S.M., Mei G., RA Bouck J., Gibbs R.A.; RT "Pediatric leukemia cDNA sequencing project."; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR RP COMPLEX. RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006; RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B., RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W., RA Conaway R.C.; RT "A set of consensus mammalian mediator subunits identified by RT multidimensional protein identification technology."; RL Mol. Cell 14:685-691(2004). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II. RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015; RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T., RA Roeder R.G.; RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation RT enriched in RNA polymerase II and is required for ER-mediated RT transcription."; RL Mol. Cell 19:89-100(2005). RN [13] RP FUNCTION, ASSOCIATION WITH PROMOTER REGIONS, INTERACTION WITH CREBBP; ESR1; RP GR; MED1; MED6; RARA; RXRA AND THRB, AND MUTAGENESIS OF LEU-646 AND RP 649-LEU-LEU-650. RX PubMed=17641689; DOI=10.1038/sj.emboj.7601797; RA Lee H.-K., Park U.-H., Kim E.-J., Um S.-J.; RT "MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid RT receptor activation."; RL EMBO J. 26:3545-3557(2007). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [15] RP STRUCTURE BY NMR OF 391-548. RX PubMed=20974256; DOI=10.1016/j.jsb.2010.10.011; RA Bontems F., Verger A., Dewitte F., Lens Z., Baert J.L., Ferreira E., RA Launoit Y.D., Sizun C., Guittet E., Villeret V., Monte D.; RT "NMR structure of the human Mediator MED25 ACID domain."; RL J. Struct. Biol. 174:245-251(2011). RN [16] RP VARIANT CMT2B2 VAL-335. RX PubMed=19290556; DOI=10.1007/s10048-009-0183-3; RA Leal A., Huehne K., Bauer F., Sticht H., Berger P., Suter U., Morera B., RA Del Valle G., Lupski J.R., Ekici A., Pasutto F., Endele S., Barrantes R., RA Berghoff C., Berghoff M., Neundoerfer B., Heuss D., Dorn T., Young P., RA Santolin L., Uhlmann T., Meisterernst M., Sereda M.W., Sereda M., RA Stassart R.M., Zu Horste G.M., Nave K.A., Reis A., Rautenstrauss B.; RT "Identification of the variant Ala335Val of MED25 as responsible for RT CMT2B2: molecular data, functional studies of the SH3 recognition motif and RT correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal RT models."; RL Neurogenetics 10:275-287(2009). RN [17] RP ERRATUM OF PUBMED:19290556. RA Leal A., Huehne K., Bauer F., Sticht H., Berger P., Suter U., Morera B., RA Del Valle G., Lupski J.R., Ekici A., Pasutto F., Endele S., Barrantes R., RA Berghoff C., Berghoff M., Neundoerfer B., Heuss D., Dorn T., Young P., RA Santolin L., Uhlmann T., Meisterernst M., Sereda M.W., Sereda M., RA Stassart R.M., Zu Horste G.M., Nave K.A., Reis A., Rautenstrauss B.; RL Neurogenetics 10:375-376(2009). RN [18] RP INVOLVEMENT IN BVSYS, VARIANT BVSYS CYS-39, AND CHARACTERIZATION OF VARIANT RP BVSYS CYS-39. RX PubMed=25792360; DOI=10.1007/s00439-015-1541-x; RA Basel-Vanagaite L., Smirin-Yosef P., Essakow J.L., Tzur S., Lagovsky I., RA Maya I., Pasmanik-Chor M., Yeheskel A., Konen O., Orenstein N., RA Weisz Hubshman M., Drasinover V., Magal N., Peretz Amit G., Zalzstein Y., RA Zeharia A., Shohat M., Straussberg R., Monte D., Salmon-Divon M., RA Behar D.M.; RT "Homozygous MED25 mutation implicated in eye-intellectual disability RT syndrome."; RL Hum. Genet. 134:577-587(2015). RN [19] RP VARIANT TRP-140. RX PubMed=25527630; DOI=10.1136/jmedgenet-2014-102793; RA Figueiredo T., Melo U.S., Pessoa A.L., Nobrega P.R., Kitajima J.P., RA Correa I., Zatz M., Kok F., Santos S.; RT "Homozygous missense mutation in MED25 segregates with syndromic RT intellectual disability in a large consanguineous family."; RL J. Med. Genet. 52:123-127(2015). CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in CC the regulated transcription of nearly all RNA polymerase II-dependent CC genes. Mediator functions as a bridge to convey information from gene- CC specific regulatory proteins to the basal RNA polymerase II CC transcription machinery. Mediator is recruited to promoters by direct CC interactions with regulatory proteins and serves as a scaffold for the CC assembly of a functional preinitiation complex with RNA polymerase II CC and the general transcription factors. Required for RARA/RXRA-mediated CC transcription. {ECO:0000269|PubMed:14657022, CC ECO:0000269|PubMed:14983011, ECO:0000269|PubMed:17641689}. CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1, CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct CC module termed the CDK8 module. Mediator containing the CDK8 module is CC less active than Mediator lacking this module in supporting CC transcriptional activation. Individual preparations of the Mediator CC complex lacking one or more distinct subunits have been variously CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CREBBP. CC Interacts with ESR1, GR, RARA, RXRA and THRB in a ligand-dependent CC fashion. Binds the Herpes simplex virus activator VP16. CC {ECO:0000269|PubMed:14657022, ECO:0000269|PubMed:14983011, CC ECO:0000269|PubMed:15175163, ECO:0000269|PubMed:15989967, CC ECO:0000269|PubMed:17641689}. CC -!- INTERACTION: CC Q71SY5; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-394558, EBI-3867333; CC Q71SY5; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-394558, EBI-10213520; CC Q71SY5; O00167-2: EYA2; NbExp=3; IntAct=EBI-394558, EBI-12807776; CC Q71SY5; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-394558, EBI-12193763; CC Q71SY5; O14964: HGS; NbExp=3; IntAct=EBI-394558, EBI-740220; CC Q71SY5; Q53G59: KLHL12; NbExp=3; IntAct=EBI-394558, EBI-740929; CC Q71SY5; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-394558, EBI-12111050; CC Q71SY5; Q14847-2: LASP1; NbExp=3; IntAct=EBI-394558, EBI-9088686; CC Q71SY5; O60244: MED14; NbExp=2; IntAct=EBI-394558, EBI-394489; CC Q71SY5; Q96RN5: MED15; NbExp=2; IntAct=EBI-394558, EBI-394506; CC Q71SY5; Q9Y2X0: MED16; NbExp=3; IntAct=EBI-394558, EBI-394541; CC Q71SY5; Q9ULK4: MED23; NbExp=4; IntAct=EBI-394558, EBI-311161; CC Q71SY5; O75448: MED24; NbExp=2; IntAct=EBI-394558, EBI-394523; CC Q71SY5; Q9NZQ3-3: NCKIPSD; NbExp=3; IntAct=EBI-394558, EBI-10963850; CC Q71SY5; A1E959: ODAM; NbExp=3; IntAct=EBI-394558, EBI-5774125; CC Q71SY5; Q8TDS5: OXER1; NbExp=3; IntAct=EBI-394558, EBI-12813389; CC Q71SY5; Q9UBV8: PEF1; NbExp=3; IntAct=EBI-394558, EBI-724639; CC Q71SY5; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-394558, EBI-373552; CC Q71SY5; P10276: RARA; NbExp=10; IntAct=EBI-394558, EBI-413374; CC Q71SY5; Q92753-1: RORB; NbExp=3; IntAct=EBI-394558, EBI-18560266; CC Q71SY5; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-394558, EBI-6257312; CC Q71SY5; P19793: RXRA; NbExp=4; IntAct=EBI-394558, EBI-78598; CC Q71SY5; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-394558, EBI-748621; CC Q71SY5; P51692: STAT5B; NbExp=3; IntAct=EBI-394558, EBI-1186119; CC Q71SY5; Q92734: TFG; NbExp=3; IntAct=EBI-394558, EBI-357061; CC Q71SY5; Q08117-2: TLE5; NbExp=3; IntAct=EBI-394558, EBI-11741437; CC Q71SY5; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-394558, EBI-11975223; CC Q71SY5; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-394558, EBI-12040603; CC Q71SY5; O00308: WWP2; NbExp=3; IntAct=EBI-394558, EBI-743923; CC Q71SY5; P28700: Rxra; Xeno; NbExp=3; IntAct=EBI-394558, EBI-346715; CC Q71SY5; G8HBG2: UL48; Xeno; NbExp=5; IntAct=EBI-394558, EBI-15844956; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14657022}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q71SY5-1; Sequence=Displayed; CC Name=4; CC IsoId=Q71SY5-4; Sequence=VSP_028146; CC Name=5; CC IsoId=Q71SY5-5; Sequence=VSP_028143; CC Name=6; CC IsoId=Q71SY5-6; Sequence=VSP_047570; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Highest levels in brain, CC heart, kidney, peripheral leukocytes, placenta, skeletal muscle and CC spleen. {ECO:0000269|PubMed:14657022, ECO:0000269|PubMed:14983011}. CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2B2 (CMT2B2) CC [MIM:605589]: A recessive axonal form of Charcot-Marie-Tooth disease, a CC disorder of the peripheral nervous system, characterized by progressive CC weakness and atrophy, initially of the peroneal muscles and later of CC the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) and CC primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 CC group are characterized by signs of axonal degeneration in the absence CC of obvious myelin alterations, normal or slightly reduced nerve CC conduction velocities, and progressive distal muscle weakness and CC atrophy. {ECO:0000269|PubMed:19290556}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) [MIM:616449]: An CC autosomal recessive syndrome characterized by eye, brain, cardiac and CC palatal abnormalities as well as growth retardation, microcephaly and CC severe intellectual disability. {ECO:0000269|PubMed:25792360}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the Mediator complex subunit 25 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG15589.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAS45401.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305}; CC Sequence=CAB66680.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAB66680.1; Type=Miscellaneous discrepancy; Note=Non-canonical splice intron-exon junction.; Evidence={ECO:0000305}; CC Sequence=CAE84581.1; Type=Miscellaneous discrepancy; Note=Non-canonical splice intron-exon junction.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF261072; AAM20739.1; -; mRNA. DR EMBL; AJ617479; CAE84581.1; ALT_SEQ; mRNA. DR EMBL; AY533507; AAS45401.1; ALT_SEQ; mRNA. DR EMBL; AL136746; CAB66680.1; ALT_SEQ; mRNA. DR EMBL; EU392500; ACB88862.1; -; mRNA. DR EMBL; AK289460; BAF82149.1; -; mRNA. DR EMBL; AC006942; AAD15565.1; -; Genomic_DNA. DR EMBL; AC018766; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471177; EAW52546.1; -; Genomic_DNA. DR EMBL; BC024312; AAH24312.2; -; mRNA. DR EMBL; BC065297; AAH65297.1; -; mRNA. DR EMBL; AF283769; AAG15589.2; ALT_INIT; mRNA. DR CCDS; CCDS33075.1; -. [Q71SY5-1] DR RefSeq; NP_112235.2; NM_030973.3. [Q71SY5-1] DR PDB; 2KY6; NMR; -; A=391-553. DR PDB; 2L23; NMR; -; A=391-548. DR PDB; 2L6U; NMR; -; A=391-543. DR PDB; 2XNF; NMR; -; A=394-543. DR PDB; 7EMF; EM; 3.50 A; Y=1-747. DR PDB; 7LBM; EM; 4.80 A; 3=1-747. DR PDB; 8GXQ; EM; 5.04 A; y=1-747. DR PDB; 8GXS; EM; 4.16 A; y=1-747. DR PDBsum; 2KY6; -. DR PDBsum; 2L23; -. DR PDBsum; 2L6U; -. DR PDBsum; 2XNF; -. DR PDBsum; 7EMF; -. DR PDBsum; 7LBM; -. DR PDBsum; 8GXQ; -. DR PDBsum; 8GXS; -. DR AlphaFoldDB; Q71SY5; -. DR BMRB; Q71SY5; -. DR EMDB; EMD-23255; -. DR EMDB; EMD-31191; -. DR EMDB; EMD-34359; -. DR EMDB; EMD-34360; -. DR SMR; Q71SY5; -. DR BioGRID; 123607; 93. DR ComplexPortal; CPX-3227; Core mediator complex. DR CORUM; Q71SY5; -. DR DIP; DIP-31454N; -. DR IntAct; Q71SY5; 58. DR MINT; Q71SY5; -. DR STRING; 9606.ENSP00000326767; -. DR BindingDB; Q71SY5; -. DR ChEMBL; CHEMBL5169169; -. DR GlyGen; Q71SY5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q71SY5; -. DR PhosphoSitePlus; Q71SY5; -. DR BioMuta; MED25; -. DR DMDM; 158706143; -. DR EPD; Q71SY5; -. DR jPOST; Q71SY5; -. DR MassIVE; Q71SY5; -. DR MaxQB; Q71SY5; -. DR PaxDb; 9606-ENSP00000326767; -. DR PeptideAtlas; Q71SY5; -. DR ProteomicsDB; 68625; -. [Q71SY5-1] DR ProteomicsDB; 68628; -. [Q71SY5-4] DR ProteomicsDB; 68629; -. [Q71SY5-5] DR ProteomicsDB; 7538; -. DR Pumba; Q71SY5; -. DR Antibodypedia; 45928; 142 antibodies from 21 providers. DR DNASU; 81857; -. DR Ensembl; ENST00000312865.10; ENSP00000326767.5; ENSG00000104973.19. [Q71SY5-1] DR Ensembl; ENST00000538643.5; ENSP00000437496.1; ENSG00000104973.19. [Q71SY5-6] DR GeneID; 81857; -. DR KEGG; hsa:81857; -. DR MANE-Select; ENST00000312865.10; ENSP00000326767.5; NM_030973.4; NP_112235.2. DR UCSC; uc002ppw.3; human. [Q71SY5-1] DR AGR; HGNC:28845; -. DR CTD; 81857; -. DR DisGeNET; 81857; -. DR GeneCards; MED25; -. DR GeneReviews; MED25; -. DR HGNC; HGNC:28845; MED25. DR HPA; ENSG00000104973; Low tissue specificity. DR MalaCards; MED25; -. DR MIM; 605589; phenotype. DR MIM; 610197; gene. DR MIM; 616449; phenotype. DR neXtProt; NX_Q71SY5; -. DR OpenTargets; ENSG00000104973; -. DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability. DR Orphanet; 464738; Basel-Vanagaite-Smirin-Yosef syndrome. DR PharmGKB; PA134984839; -. DR VEuPathDB; HostDB:ENSG00000104973; -. DR eggNOG; ENOG502QRN5; Eukaryota. DR GeneTree; ENSGT00940000160439; -. DR HOGENOM; CLU_007594_0_0_1; -. DR InParanoid; Q71SY5; -. DR OMA; NDQQKIP; -. DR OrthoDB; 2916084at2759; -. DR PhylomeDB; Q71SY5; -. DR TreeFam; TF329598; -. DR PathwayCommons; Q71SY5; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR SignaLink; Q71SY5; -. DR SIGNOR; Q71SY5; -. DR BioGRID-ORCS; 81857; 175 hits in 1159 CRISPR screens. DR ChiTaRS; MED25; human. DR EvolutionaryTrace; Q71SY5; -. DR GeneWiki; MED25; -. DR GenomeRNAi; 81857; -. DR Pharos; Q71SY5; Tbio. DR PRO; PR:Q71SY5; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q71SY5; Protein. DR Bgee; ENSG00000104973; Expressed in oocyte and 185 other cell types or tissues. DR ExpressionAtlas; Q71SY5; baseline and differential. DR GO; GO:0070847; C:core mediator complex; IPI:ComplexPortal. DR GO; GO:0016592; C:mediator complex; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal. DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central. DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; IPI:UniProtKB. DR GO; GO:0046965; F:nuclear retinoid X receptor binding; IPI:UniProtKB. DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB. DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0035563; P:positive regulation of chromatin binding; IMP:UniProtKB. DR GO; GO:2001178; P:positive regulation of mediator complex assembly; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0060261; P:positive regulation of transcription initiation by RNA polymerase II; NAS:ComplexPortal. DR GO; GO:0051123; P:RNA polymerase II preinitiation complex assembly; NAS:ComplexPortal. DR Gene3D; 2.40.290.30; Mediator complex subunit 25, ACID domain; 1. DR InterPro; IPR021394; Med25_PTOV. DR InterPro; IPR038196; Med25_PTOV_sf. DR InterPro; IPR021397; Mediator_Med25_SD1. DR InterPro; IPR021419; Mediator_Med25_VWA. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR12433; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 25; 1. DR PANTHER; PTHR12433:SF10; MEDIATOR OF RNA POLYMERASE II TRANSCRIPTION SUBUNIT 25; 1. DR Pfam; PF11232; Med25; 1. DR Pfam; PF11235; Med25_SD1; 1. DR Pfam; PF11265; Med25_VWA; 1. DR SUPFAM; SSF53300; vWA-like; 1. DR Genevisible; Q71SY5; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Charcot-Marie-Tooth disease; KW Direct protein sequencing; Disease variant; Intellectual disability; KW Methylation; Neurodegeneration; Neuropathy; Nucleus; Reference proteome; KW Transcription; Transcription regulation. FT CHAIN 1..747 FT /note="Mediator of RNA polymerase II transcription subunit FT 25" FT /id="PRO_0000304952" FT REGION 1..226 FT /note="Interaction with the Mediator complex" FT REGION 233..274 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 299..390 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 389..543 FT /note="Interaction with VP16" FT REGION 395..545 FT /note="Interaction with CREBBP" FT /evidence="ECO:0000269|PubMed:17641689" FT REGION 548..747 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 564..653 FT /note="Interaction with RARA" FT /evidence="ECO:0000269|PubMed:17641689" FT REGION 640..707 FT /note="Interaction with RARA" FT /evidence="ECO:0000269|PubMed:17641689" FT MOTIF 646..650 FT /note="LXXLL motif" FT COMPBIAS 319..345 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 577..607 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 608..638 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 649..712 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 725 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q8VCB2" FT VAR_SEQ 61..273 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_047570" FT VAR_SEQ 303..319 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028143" FT VAR_SEQ 716..747 FT /note="GQMLLSGGPRGPVPQPGLQPSVMEDDILMDLI -> AAKRKREGEGRVFREK FT WERAYFFVEVKSMPMCLICKQIVSVLKEYNLKRHYESKHSKSYDQYTEQTRRIRARPIW FT PDP (in isoform 4)" FT /evidence="ECO:0000303|Ref.10" FT /id="VSP_028146" FT VARIANT 39 FT /note="Y -> C (in BVSYS; the mutation impairs interaction FT with the Mediator complex; dbSNP:rs794729668)" FT /evidence="ECO:0000269|PubMed:25792360" FT /id="VAR_073949" FT VARIANT 140 FT /note="R -> W (found in a patient with syndromic FT intellectual disability; uncertain significance; FT dbSNP:rs781140315)" FT /evidence="ECO:0000269|PubMed:25527630" FT /id="VAR_073950" FT VARIANT 335 FT /note="A -> V (in CMT2B2; dbSNP:rs145770066)" FT /evidence="ECO:0000269|PubMed:19290556" FT /id="VAR_063521" FT MUTAGEN 646 FT /note="L->A: Abrogates interaction with RARA." FT /evidence="ECO:0000269|PubMed:17641689" FT MUTAGEN 649..650 FT /note="LL->AA: Abrogates interaction with RARA." FT /evidence="ECO:0000269|PubMed:17641689" FT CONFLICT 20 FT /note="F -> S (in Ref. 1; AAM20739)" FT /evidence="ECO:0000305" FT CONFLICT 236 FT /note="P -> L (in Ref. 2; CAE84581 and 4; CAB66680)" FT /evidence="ECO:0000305" FT CONFLICT 268 FT /note="V -> I (in Ref. 1; AAM20739)" FT /evidence="ECO:0000305" FT CONFLICT 514 FT /note="L -> M (in Ref. 3; AAS45401)" FT /evidence="ECO:0000305" FT CONFLICT 536 FT /note="G -> D (in Ref. 3; AAS45401)" FT /evidence="ECO:0000305" FT CONFLICT 703 FT /note="S -> F (in Ref. 1; AAM20739)" FT /evidence="ECO:0000305" FT STRAND 16..23 FT /evidence="ECO:0007829|PDB:7EMF" FT TURN 27..31 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 32..38 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 40..47 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 61..63 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 65..71 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 91..100 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 114..131 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 139..145 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 166..174 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 175..177 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 179..186 FT /evidence="ECO:0007829|PDB:7EMF" FT HELIX 189..197 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 215..218 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 220..226 FT /evidence="ECO:0007829|PDB:7EMF" FT STRAND 396..409 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 414..417 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 424..434 FT /evidence="ECO:0007829|PDB:2KY6" FT HELIX 441..443 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 446..454 FT /evidence="ECO:0007829|PDB:2KY6" FT HELIX 455..461 FT /evidence="ECO:0007829|PDB:2KY6" FT HELIX 462..465 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 466..475 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 476..478 FT /evidence="ECO:0007829|PDB:2L6U" FT HELIX 480..493 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 494..499 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 502..504 FT /evidence="ECO:0007829|PDB:2L23" FT STRAND 510..515 FT /evidence="ECO:0007829|PDB:2KY6" FT TURN 517..519 FT /evidence="ECO:0007829|PDB:2KY6" FT STRAND 521..529 FT /evidence="ECO:0007829|PDB:2KY6" FT HELIX 530..545 FT /evidence="ECO:0007829|PDB:2KY6" SQ SEQUENCE 747 AA; 78171 MW; 6FE13FB45786402D CRC64; MVPGSEGPAR AGSVVADVVF VIEGTANLGP YFEGLRKHYL LPAIEYFNGG PPAETDFGGD YGGTQYSLVV FNTVDCAPES YVQCHAPTSS AYEFVTWLDG IKFMGGGGES CSLIAEGLST ALQLFDDFKK MREQIGQTHR VCLLICNSPP YLLPAVESTT YSGCTTENLV QQIGERGIHF SIVSPRKLPA LRLLFEKAAP PALLEPLQPP TDVSQDPRHM VLVRGLVLPV GGGSAPGPLQ SKQPVPLPPA APSGATLSAA PQQPLPPVPP QYQVPGNLSA AQVAAQNAVE AAKNQKAGLG PRFSPITPLQ QAAPGVGPPF SQAPAPQLPP GPPGAPKPPP ASQPSLVSTV APGSGLAPTA QPGAPSMAGT VAPGGVSGPS PAQLGAPALG GQQSVSNKLL AWSGVLEWQE KPKPASVDAN TKLTRSLPCQ VYVNHGENLK TEQWPQKLIM QLIPQQLLTT LGPLFRNSRM VQFHFTNKDL ESLKGLYRIM GNGFAGCVHF PHTAPCEVRV LMLLYSSKKK IFMGLIPYDQ SGFVNGIRQV ITNHKQVQQQ KLEQQQRGMG GQQAPPGLGP ILEDQARPSQ NLLQLRPPQP QPQGTVGASG ATGQPQPQGT AQPPPGAPQG PPGAASGPPP PGPILRPQNP GANPQLRSLL LNPPPPQTGV PPPQASLHHL QPPGAPALLP PPHQGLGQPQ LGPPLLHPPP AQSWPAQLPP RAPLPGQMLL SGGPRGPVPQ PGLQPSVMED DILMDLI //